Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model

Gábor Szabó, Levente Fazekas, Susanne Bährle, Damian MacDonald, Nicole Stumpf, Christian F. Vahl, Siegfried Hagl

Research output: Article

34 Citations (Scopus)

Abstract

Objective: Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. Methods: Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 μmol/kg/min), BQ788 (3 μmol/kg/min), ET-1 (8 pmol/kg/min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n = 1.2. each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after I and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. Results: Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups (p<0.05). Conclusions: These results suggest that endogenous ET release is involved in the pathogenesis of reperfusion injury after heart transplantation. ET-A and ET-B receptor antagonists may be useful to reduce ischemia/reperfusion injury.

Original languageEnglish
Pages (from-to)683-690
Number of pages8
JournalCardiovascular research
Volume39
Issue number3
DOIs
Publication statusPublished - szept. 1 1998

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ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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